The objectives of the proposed research are to identify the neuronal systems which subserve acute responses to opiates as well as the long term effects of tolerance and dependence. One strategy will be to use a developmental approach. The onset in ontogeny of acute inhibitory responses of the guinea pig ileum to opiates as well as the earliest stage in ontogeny during which opiate tolerance and dependency can develop will be determined. The onset of opiate responses will be correlated with the previously determined sequence of development of known enteric neurotransmitters. The role of endorphins in the developmental process will also be determined. In addition the neurotransmitters that are involved in mediating both the formation and manifestation of withdrawal from opiates will be investigated.